Biphenyl sulfonamide compounds for the treatment of kidney diseases or disorders

Abstract

Methods of treatment comprising administering a compound having structure (I),or a pharmaceutically acceptable salt thereof, or administering a pharmaceutical composition comprising the compound of structure (I) or pharmaceutically acceptable salt thereof, are provided.

1 .- 44 . (canceled) 
     
     
         45 . A method of treating a kidney disease or disorder comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound having structure (I), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein said subject has a urine protein to creatinine (“UP/C”) ratio greater than 1.5 g/g prior to administration of said pharmaceutical composition. 
       
     
     
         46 . The method according to  claim 45 , wherein said subject has an estimated glomerular filtration rate greater than 30 ml/min prior to administration of said pharmaceutical composition. 
     
     
         47 . The method according to  claim 45 , wherein said pharmaceutical composition is administered to said subject
 (i) in an amount sufficient to achieve a UP/C ratio of less than or equal to 1.5 g/g; or   (ii) at a dosing regimen sufficient to achieve a UP/C ratio of less than or equal to 1.5 g/g.   
     
     
         48 . The method according to  claim 45 , wherein said pharmaceutical composition is administered to said subject over an administration period in an amount sufficient to achieve a UP/C ratio of less than or equal to 1.5 g/g for at least a portion of said administration period. 
     
     
         49 . The method according to  claim 45 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is from about 50 mg/day to about 1000 mg/day. 
     
     
         50 . The method according to  claim 45 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is from 200 mg/day to 800 mg/day. 
     
     
         51 . The method according to  claim 45 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is 200 mg/day. 
     
     
         52 . The method according to  claim 45 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is 400 mg/day. 
     
     
         53 . The method according to  claim 45 , wherein the amount of said compound having structure (I), or pharmaceutically acceptable salt thereof, administered to said subject is 800 mg/day. 
     
     
         54 . The method according to  claim 45 , wherein said administering comprises administering said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at an initial dose and administering said compound having structure (I), or a pharmaceutically acceptable salt thereof, to said subject at a subsequent dose, wherein said subsequent dose is greater than said initial dose. 
     
     
         55 . The method according to  claim 54 , wherein said initial dose is 400 mg/day and said subsequent dose is 800 mg/day. 
     
     
         56 . The method according to  claim 54 , wherein said initial dose is 200 mg/day and said subsequent dose is 400 mg/day. 
     
     
         57 . The method according to  claim 56 , wherein said subject is a child weighing less than 50 kg. 
     
     
         58 . The method according to  claim 54 , wherein said initial dose is administered for a period of 2 weeks. 
     
     
         59 . The method according to  claim 54 , wherein the method further comprises measuring the blood pressure of said subject before administering said subsequent dose. 
     
     
         60 . The method according to  claim 45 , wherein said compound has structure (I). 
     
     
         61 . The method according to  claim 45 , further comprising administering to said subject one or more additional therapeutic agents. 
     
     
         62 . The method according to  claim 45 , wherein said kidney disease or disorder is a disorder related to glomerular function. 
     
     
         63 . The method according to  claim 45 , wherein said kidney disease or disorder is focal segmental glomerulosclerosis (FSGS). 
     
     
         64 . The method according to  claim 63 , wherein said FSGS is primary FSGS. 
     
     
         65 . The method according to  claim 63 , wherein said FSGS is secondary FSGS. 
     
     
         66 . The method according to  claim 63 , wherein said FSGS is genetic FSGS. 
     
     
         67 . The method according to  claim 45 , wherein said kidney disease or disorder is IgA nephropathy. 
     
     
         68 . The method according to  claim 45 , wherein said kidney disease or disorder is idiopathic membranous nephropathy (IMN). 
     
     
         69 . The method according to  claim 45 , wherein said kidney disease or disorder is diabetic nephropathy. 
     
     
         70 . The method according to  claim 45 , wherein said kidney disease or disorder is lupus nephritis.